scholarly journals Solvent Effect on Dipeptide Bond Formation: Glycine as a Case Study

2019 ◽  
Author(s):  
Sofiene Achour ◽  
Zied Hosni ◽  
Sarra Darghouth ◽  
Christopher Syme
Keyword(s):  
Density Functional ◽  
Bond Formation ◽  
Peptide Bond ◽  
Point Of View ◽  
Basis Sets ◽  
Peptide Bond Formation ◽  
Peptide Bonds ◽  
Governing Factor ◽  
Solvent Molecules

Peptide bond formation is a crucial chemical process that dominates most biological mechanisms and is claimed to be a governing factor in the origin of life. Dipeptides made from glycine are studied computationally via Density Functional Theory (DFT) using two different basis sets. This reaction was investigated from both a thermodynamic and kinetic point of view. The effect of explicit solvation via the introduction of discreet solvent molecules was investigated. Water, methanol, and cyclohexane were all employed as solvent media in addition to gas to investigate their effects on the mechanism of peptide bond formation. This computational investigation revealed that methanol is slightly better than water to leverage peptide bond formation both kinetically and thermodynamically, while cyclohexane, a non-polar and non-protic solvent, is the least effective after gas as a medium of solvation. Energetic results in the gas environment are very close to those obtained in polar and protic solvents, suggesting that peptide bonds can be formed under interstellar conditions.

Solvent Effect on Dipeptide Bond Formation: Glycine as a Case Study

2019 ◽  
Author(s):  
Sofiene Achour ◽  
Zied Hosni ◽  
Sarra Darghouth ◽  
Christopher Syme
Keyword(s):  
Density Functional ◽  
Bond Formation ◽  
Peptide Bond ◽  
Point Of View ◽  
Basis Sets ◽  
Peptide Bond Formation ◽  
Peptide Bonds ◽  
Governing Factor ◽  
Solvent Molecules

Peptide bond formation is a crucial chemical process that dominates most biological mechanisms and is claimed to be a governing factor in the origin of life. Dipeptides made from glycine are studied computationally via Density Functional Theory (DFT) using two different basis sets. This reaction was investigated from both a thermodynamic and kinetic point of view. The effect of explicit solvation via the introduction of discreet solvent molecules was investigated. Water, methanol, and cyclohexane were all employed as solvent media in addition to gas to investigate their effects on the mechanism of peptide bond formation. This computational investigation revealed that methanol is slightly better than water to leverage peptide bond formation both kinetically and thermodynamically, while cyclohexane, a non-polar and non-protic solvent, is the least effective after gas as a medium of solvation. Energetic results in the gas environment are very close to those obtained in polar and protic solvents, suggesting that peptide bonds can be formed under interstellar conditions.

scholarly journals Prebiotic Peptide Bond Formation Through Amino Acid Phosphorylation. Insights from Quantum Chemical Simulations

Life ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 75 ◽  
Author(s):  
Berta Martínez-Bachs ◽  
Albert Rimola
Keyword(s):  
Free Energy ◽  
Quantum Chemical ◽  
Density Functional ◽  
Bond Formation ◽  
Building Blocks ◽  
Peptide Bond ◽  
High Energy ◽  
Free Energy Barrier ◽  
Peptide Bond Formation ◽  
Condensation Reactions

Condensation reactions between biomolecular building blocks are the main synthetic channels to build biopolymers. However, under highly diluted prebiotic conditions, condensations are thermodynamically hampered since they release water. Moreover, these reactions are also kinetically hindered as, in the absence of any catalyst, they present high activation energies. In living organisms, in the formation of peptides by condensation of amino acids, this issue is overcome by the participation of adenosine triphosphate (ATP), in which, previous to the condensation, phosphorylation of one of the reactants is carried out to convert it as an activated intermediate. In this work, we present for the first time results based on density functional theory (DFT) calculations on the peptide bond formation between two glycine (Gly) molecules adopting this phosphorylation-based mechanism considering a prebiotic context. Here, ATP has been modeled by a triphosphate (TP) component, and different scenarios have been considered: (i) gas-phase conditions, (ii) in the presence of a Mg2+ ion available within the layer of clays, and (iii) in the presence of a Mg2+ ion in watery environments. For all of them, the free energy profiles have been fully characterized. Energetics derived from the quantum chemical calculations indicate that none of the processes seem to be feasible in the prebiotic context. In scenarios (i) and (ii), the reactions are inhibited due to unfavorable thermodynamics associated with the formation of high energy intermediates, while in scenario (iii), the reaction is inhibited due to the high free energy barrier associated with the condensation reactions. As a final consideration, the role of clays in this TP-mediated peptide bond formation route is advocated, since the interaction of the phosphorylated intermediate with the internal clay surfaces could well favor the reaction free energies.

On Ribosome Conservation and Evolution

2006 ◽  
Vol 52 (3-4) ◽  
pp. 359-374 ◽  
Author(s):  
Ilana Agmon ◽  
Anat Bashan ◽  
Ada Yonath
Keyword(s):  
Bond Formation ◽  
Peptide Bond ◽  
Binding Modes ◽  
Peptide Bond Formation ◽  
Peptidyl Transferase ◽  
Peptide Bonds ◽  
Peptidyl Transferase Center ◽  
Enzymatic Function ◽  
Rotatory Motion ◽  
Rna Fold

The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC), is situated within a highly conserved universal symmetrical region that connects all ribosomal functional centers involved in amino acid polymerization. The linkage between this elaborate architecture and A-site tRNA position revealed that the A-> P-site passage of the tRNA terminus in the peptidyl transferase center is performed by a rotatory motion, synchronized with the overall tRNA/mRNA sideways movement. Guided by the PTC, the rotatory motion leads to stereochemistry suitable for peptide bond formation, as well as for substrate-mediated catalysis, consistent with quantum mechanical calculations elucidating the transition state mechanism for peptide bond formation and indicating that the peptide bond is being formed during the rotatory motion. Analysis of substrate binding modes to inactive and active ribosomes illuminated the significant PTC mobility and supported the hypothesis that the ancient ribosome produced single peptide bonds and non-coded chains, utilizing free amino acids. Genetic control of the reaction evolved after poly-peptides capable of enzymatic function were created, and an ancient stable RNA fold was converted into tRNA molecules. As the symmetry relates only the backbone fold and nucleotide orientations, but not nucleotide sequence, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC has evolved by gene fusion, presumably by taking advantage of similar RNA fold structures.

Quantum mechanical tunnelling through the catalytic effects of A2451 ribosomal residue during a stepwise peptide bond formation

2019 ◽  
Vol 97 (4) ◽  
pp. 497-503
Author(s):  
Hadieh Monajemi ◽  
Sharifuddin Md. Zain ◽  
Toshimasa Ishida ◽  
Wan Ahmad Tajuddin Wan Abdullah
Keyword(s):  
Reaction Mechanism ◽  
Proton Transfer ◽  
Density Functional ◽  
Bond Formation ◽  
Peptide Bond ◽  
State Theory ◽  
Basis Set ◽  
Quantum Mechanical ◽  
Peptide Bond Formation ◽  
Quantum Mechanical Effects

The search for the mechanism of ribosomal peptide bond formation is still ongoing. Even though the actual mechanism of peptide bod formation is still unknown, the dominance of proton transfer in this reaction is known for certain. Therefore, it is vital to take the quantum mechanical effects on proton transfer reaction into consideration; the effects of which were neglected in all previous studies. In this study, we have taken such effects into consideration using a semi-classical approach to the overall reaction mechanism. The M06-2X density functional with the 6-31++G(d,p) basis set was used to calculate the energies of the critical points on the potential energy surface of the reaction mechanism, which are then used in transition state theory to calculate the classical reaction rate. The tunnelling contribution is then added to the classical part by calculating the transmission permeability and tunnelling constant of the reaction barrier, using the numerical integration over the Boltzmann distribution for the symmetrical Eckart potential. The results of this study, which accounts for quantum effects, indicates that the A2451 ribosomal residue induces proton tunnelling in a stepwise peptide bond formation.

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